The Blame Game

"Our lyophilizers had vent filters to protect the product within the chamber," explains our GMP Agent-in-Place. "Every six months we tested those vent filters, and unless they were physically damaged, we never had a failure?until this one time. We checked the usual suspects, especially the seals for the vent filter casing, because they are often the cause of a false test reading. We even recalibrated the test apparatus, all to no avail.

"Destructive inspection of the filter showed some sort of oily material that was identified in the laboratory as the silicone fluid used to transfer heat within the chamber. Our maintenance staff then inspected the piping in the lyophilizer chamber and finally found a pin-hole leak.

"Although that solved the vent-filter-failure problem, it raised product contamination issues for all batches made since the last passing test. Arggggh! We ended up doing a simulation run with the leaking pipe to measure analytically the extent of the contamination."

Soaked to fit

"We had high hopes for a product we had purchased," reports our GMP Agent-in-Place. "We thought we could sell 10 times the amount the current product owner was selling. It was a strange time-release formula, however. First, the beads were made in a coating pan. Then the beads were processed through a tablet press to create the time-release tablets.

"Although we thought it strange, the batch records we received seemed straightforward enough. That was, until we tried it. No matter what we tried, we couldn't get a dissolution profile matching that of the original manufacturer. The beads usually powdered during compression and the product released too quickly. We were starting to suspect the original manufacturer's testing was faked.

"Finally, a desperate manufacturing manager convinced the original manufacturer to allow him to watch the process at their site. Their solution to the problem was simple: They just didn't dry the beads completely in the coating pans, and if they had to store the beads overnight, they were stored in sealed containers. The secret was compressing the beads while they were wet."

The computer did it

"A batch passed our internal quality review, all the in-process and final product testing passed, and FDA had issued a lot release for the batch," notes our GMP Agent-in-Place. "So why didn't the quality personnel release it to ship? This must have been what the distribution center was asking itself.

"Apparently, an employee had sufficient computer access to release the batch, even though he was not authorized to do so. You see, the lot was waiting for the SBE-30 date to pass, so it really wasn't ready for release after all. Oops!

"We discussed this situation with FDA, issued a Biological Product Deviation Report, and now are anxiously awaiting an inspection."

Pharmaceutical archeology

"The company parking lot needed to be expanded, so it was decided to move our back fence another 100 feet back," notes our GMP Agent-in-Place. "But when we dug up the old fence, we found thousands of 20-year-old full-product vials.

"It appeared that a rejected lot was buried on the site illegally. We are still not sure why, but we had to probe the rest of the back lot to determine whether there were more of these 'ancient burial grounds.'"

Pharmaceutical Technology's monthly "Agent-in-Place" column distills true-life cautionary tales from the secret files of Control, a senior compliance officer. If you have a story of clueless operators, oblivious management, inopportune lapses of judgment, or Murphy's Law in action, please send it to Control at AgentinPlace@advanstar.com We won't use any names, but if we do use your tale of disaster, courage, or just plain weirdness, Control will send you a coveted Pharmaceutical Technology t-shirt.